报告题目：Decoding Tumor-induced Intercellular Communicaiton in Drosophila

报告时间：2026年11月4日14：30-16：00

报告地点：生命科学学院7幢301报告厅

报告专家：马仙珏 西湖大学 特聘研究员/长聘副教授

报告人简介

马仙珏（1987-），西湖大学未来生物医药学院副院长。2009年与2014年分别在同济大学获得本科与博士学位；2014年至2019年先后在美国约翰霍普金斯大学医学院（HHMI）和耶鲁大学医学院(HHMI)从事博士后研究。2019 年6 月全职回到西湖大学生命科学学院，担任特聘研究员，并于2025 年晋升为长聘岗。长期深耕于肿瘤细胞通讯、信号转导及组织稳态调控领域，致力于解析从细胞内网络整合到细胞间/器官间互作驱动肿瘤发生发展的分子机制。近年来，申请人带领课题组创新性地利用果蝇遗传学模型、哺乳动物体系及跨物种分析框架，在肿瘤异质性演化、细胞竞争机制及微环境重塑等方面取得了一系列原创性成果。自2019 年以来，申请人以通讯作者（含共通讯）身份在Cell Res, Dev Cell, EMBO J, PNAS, Signal Transduction and Target Therapy, Cell Rep, Oncogene等国际主流期刊发表系列论文。主持国家自然科学基金优秀青年科学基金项目、面上项目，以及浙江省自然科学基金重大项目、杭州市重点项目等多项国家级及省部级课题。曾获得上海市科技进步一等奖、二等奖，Cells 2024 Young Investigator Award，2023年Sanofi-Cell Research Outstanding Paper Award及杭州市教育局系统优秀教师等荣誉。

报告摘要

Tumorigenesis is a complex biological process involving intricate interactions among multiple cell types, signaling pathways, and the microenvironment. During this process, intercellular communication plays central roles, profoundly influencing key steps in tumorigenesis, including tumor initiation, progression, metastasis, and immune evasion. Here, we uncover a novel tumor-promoting form of cell competition wherein malignant clones hijack interclonal Hedgehog (Hh) and Wnt signaling to convert competitive pressure into a pro-tumorigenic force. We find that Pp1-87B depleted, RAS-mutant “loser” cells undergo Hh-mediated apoptosis while secreting Wingless (Wg). This paracrine Wg signal hyperactivate β-catenin in neighboring RAS “winner” clones, reprogramming them into invasive super-competitors. This mechanism is conserved in human pancreatic ductal adenocarcinoma (PDAC), where PPP1CA loss in KRAS-mutant cells induces analogous Hh-Wnt synergy, accelerating tumor growth in mouse xenograft models and correlating with clonal selection in patient specimens. Our study elucidates a paradoxical role for cell competition in intratumoral heterogeneity, where distinct tumor clones across species exploit conserved developmental signaling pathways to fuel malignancy. These findings establish interclonal communication as a critical driver of tumor ecosystem dynamics and identify Hh-Wnt crosstalk as a promising therapeutic vulnerability in heterogeneous cancers.

代表性论文

1. Kong, D.#, Lin, P.#, Guo, Y.#, Zhao, S.#, Lin, K.#, Yang, S.#, Zhu, G., Xie, L., Tatekawa, S., Zheng, J., Xu, W., He, L., Ishii, H., Jin, B.*, Cheng, K.*, Xie, Q*, Ma, X.* (2026) Tumors exploit interclonal Hedgehog-Wnt crosstalk to drive tumor-promoting cell competition. Dev Cell, 61(9):1915-1933.

2. Guo, Y.#, Zheng, J.#, Wu, Y., Zhao, K., Lv, D., Liu, W., Wang, M., Xu, W., Lu, J., Wang, X.*, Ma, X.* (2026) Evolutionarily conserved oncogenic mechanisms revealed by ART-D: cross-species insights from Drosophila tumors to human cancers. Mol. Syst. Biol. (Cover story), 22(8):1214-1251.

3.  Song, S.#, Bian, W.#, Chen, X.#, Miao, D.#, Huang, Z., Guo, P., Mu, J., Yang, S., Yan, D., Xu, W., Zhou, X., Yun, Y., Zhang, Q.*, Li, X.*, Yang, P.*, Ma, X.* Phase separated RBM15-NICD condensates couple m6A modification to oncogenic transcription in Notch-driven oncogenesis. Signal Transduction and Targeted Therapy (in press)

4. Kong, D.#*, Li, X.#, Zhao, S.#, Wang, C.#, Cai, Z., Song, S., Guo, Y., Kuang, X., Wang, X., Liu, W., Liu, P., Guo, X., Xu, W., Wang, Y., Zhao, B., Jin, B.*, He, L.*, Ma, X.* (2025) Adipose tissue-secreted Spz5 promotes distal tumor progression via Toll-6-mediated Hh pathway activation in Drosophila. EMBO J, 44(15):4301-4330.

5．Zhao, S.#, Guo, Y.#, Kuang, X., Li, X., Wu, C., Lin, P., Xie, Q., Zhai, Z., Kong, D.*, Ma, X.* (2025) Hemocytes facilitate interclonal cooperation-induced tumor malignancy by hijacking the innate immune system in Drosophila. EMBO J, 44(19):5394-5428.